Shape memory polymer vessel occlusion device

ABSTRACT

An embodiment includes a system comprising: an outer conduit; a shape memory polymer (SMP) foam; a metal backbone including: (a)(i) a first portion that extends from the SMP foam proximal end to the SMP foam distal end and which is generally covered by the SMP foam, and (a)(ii) a distal portion that extends distally from the SMP foam distal end and which is not covered by the SMP foam; wherein: (b)(i) SMP foam and the metal backbone are both included within the outer conduit adjacent to the outer conduit distal end; (b)(ii) the metal backbone distal portion transitions from a secondary shape that is uncoiled to a primary shape that is coiled; and (b)(iii) the metal backbone distal portion is in the metal backbone distal portion secondary shape and is located between the SMP foam distal end and the distal end of the outer conduit.

PRIORITY CLAIM

This application claims priority to U.S. Provisional Patent ApplicationNo. 62/214,767 filed on Sep. 4, 2015 and entitled “Shape Memory PolymerVessel Occlusion Device”, the content of which is hereby incorporated byreference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was made with government support under R01EB000462awarded by National Institutes of Health National Institute ofBiomedical Imaging and Bioengineering. The government has certain rightsin the invention

BACKGROUND

An estimated 6 million people in the United States suffer from severesymptoms of chronic venous insufficiency. Symptoms range from dramaticskin changes to painful recalcitrant ulcers that are often found in thelower extremities. Chronic venous insufficiency is caused by weakenedvenous valves that can no longer prevent backflow in peripheral veinsthat carry blood to the heart resulting in a sudden rise in venouspressure. This hypertension can lead to the formation of varicose veinsas well as venous ulcers. The greater saphenous vein is the most commonregion treated for chronic venous insufficiency. Previous methods oftreatment of the manifestations of chronic venous insufficiency includemanual compression, surgical ligation and stripping, sclerotherapy, andendovenous ablation of the greater saphenous vein. Endovenous ablationhas many downfalls. With endovenous ablation the patient experiencespain, either from the anesthetic injections or from the laser treatment.Further, recanalization may occur as the physician must uniformly ablatethe whole cross-section of the vein and control the laser's pull-backspeed. Many other complications may result such as deep vein thrombosis,bruising, dysesthesia, skin burns, bruising, thrombophlebitis, and nervedamage.

BRIEF DESCRIPTION OF THE DRAWINGS

Features and advantages of embodiments of the present invention willbecome apparent from the appended claims, the following detaileddescription of one or more example embodiments, and the correspondingfigures. Where considered appropriate, reference labels have beenrepeated among the figures to indicate corresponding or analogouselements.

FIGS. 1(A)-(C) and (D)-(F) depict deployment of embodiments.

FIGS. 2(A)-(F) depict deployment of embodiments.

FIGS. 3(A)-(B) depict a shape memory polymer foam with an anchor in preand post expansion conditions.

FIGS. 4(A)-(B) depict a shape memory polymer foam with an anchor in preand post expansion conditions.

FIGS. 5(A)-(B) depict a shape memory polymer foam with dual anchors inpre and post expansion conditions.

FIG. 6 depicts an embodiment including flower shaped anchors.

FIG. 7 shows thermomechanical analysis of various foam formulations.

FIGS. 8(A)-(B) depict a shape memory polymer foam on a coil in pre andpost expansion conditions.

FIG. 9 depicts a shape memory polymer foam on a coil.

FIG. 10 depicts a shape memory polymer foam on a conical coil.

FIG. 11 depicts an image of an embodiment before the anchor of theembodiment has fully deployed.

FIGS. 12(A)-(E) depict deployment of an embodiment.

DETAILED DESCRIPTION

Reference will now be made to the drawings wherein like structures maybe provided with like suffix reference designations. In order to showthe structures of various embodiments more clearly, the drawingsincluded herein are diagrammatic representations of structures. Thus,the actual appearance of the fabricated structures, for example in aphotomicrograph, may appear different while still incorporating theclaimed structures of the illustrated embodiments. Moreover, thedrawings may only show the structures useful to understand theillustrated embodiments. Additional structures known in the art may nothave been included to maintain the clarity of the drawings. “Anembodiment”, “various embodiments” and the like indicate embodiment(s)so described may include particular features, structures, orcharacteristics, but not every embodiment necessarily includes theparticular features, structures, or characteristics. Some embodimentsmay have some, all, or none of the features described for otherembodiments. “First”, “second”, “third” and the like describe a commonobject and indicate different instances of like objects are beingreferred to. Such adjectives do not imply objects so described must bein a given sequence, either temporally, spatially, in ranking, or in anyother manner. “Connected” may indicate elements are in direct physicalor electrical contact with each other and “coupled” may indicateelements co-operate or interact with each other, but they may or may notbe in direct physical or electrical contact.

An embodiment provides a minimally invasive approach to achieve completeocclusion of arteries and veins within the peripheral vasculature. Thecost, complexity, recurrence, risk, and complications of peripheralembolizations make the embodiments discussed herein highly desirable.

An embodiment uses polyurethane shape memory polymer (SMP) foam toselectively occlude regions of vasculature where persistent blood flowmay cause complications. The morphology and chemistry of the foam allowsit to be compressed and loaded into an introducer and advanced through acatheter to the target region. Upon contact with circulating blood, thefoam expands (e.g., within 2, 4, 6, 8, or 10 minutes after contactingblood) to its original geometry and completely fills the vessel lumen.The procedure utilizes minimally invasive techniques.

An embodiment includes one or more anchors placed proximal, distal, orat both locations relative to the device. The anchor(s) holds the devicein place within the blood vessel. In certain embodiments, the anchor(s)is made of nitinol and/or platinum alloys.

Additionally, in an embodiment an object (e.g., catheter, expandingballoon catheter) is used to guide the device to the location (at theurging of a guide wire) in the blood vessel requiring treatment. Thisallows for the device to fully expand within the vessel with minimalblood flow to the location of the implant.

An embodiment of the SMP vessel occlusion device may utilize a number ofdelivery mechanisms. One such mechanism is a core wire that is placedwithin the volume of the foam implant and the implant is crimped overthe core wire to create friction between the implant and core wire. Thefriction allows retraction and advancement of the device until it isfully expanded in the lumen of the treatment vessel. Once the device isfully expanded the friction is reduced enough to allow the core wire tobe retracted through the volume of the device.

Another such delivery mechanism is one in which the device is simplyadvanced through the catheter with a guidewire or pusher mechanism untilthe device is completely ejected from the delivery catheter. Such anembodiment may only include the foam without a core wire. The embodimentmay be coupled with an anchor(s) (e.g., nitinol mesh) implantedseparately from the foam upstream and/or downstream of the foam.

Another delivery mechanism is one in which the proximal end of thedevice is attached to a pusher mechanism via an exposed stainless steelwire. When the device is delivered to the target vessel, an electricalcurrent is applied to the pusher mechanism which causes electrolysis ofthe exposed stainless steel wire-effectively releasing the implant fromthe pusher mechanism.

Embodiments of vascular occlusion devices discussed herein have a widevariety of indications, including the management of pelvic venouscongestion, varicocele, varicosities associated with portal veinhypertension, traumatic hemorrhage, splenic artery aneurysms, andchronic venous insufficiency (CVI). In each of these conditions, bloodflow through specific vascular pathways presents potentiallylife-threatening consequences and extreme amounts of pain. In theseinstances, physicians rely on occlusive devices to divert blood flowfrom susceptible vessels and minimize adverse outcomes. More generally,embodiments are useful for solve any manner of vascular issue brought onby a vascular anomaly. Even more generally, the foam systems may be usedto block flow in non-biological contexts. For example, foams (coupled toone or more anchors in some embodiments) may be used in general plumbingcontexts or to otherwise quickly block fluid flow (where fluid flow mayentail liquid or gas state flow).

An embodiment is directed to an embolic device, wherein the device isused to stably occlude the flow of blood within a vessel undergoingtreatment. In the embodiment, the clot formation and stable occlusionoccurs within 0-30 minutes after deployment of the device. For example,based on HDI content occlusion may occur in less than 60 seconds fromthe time the foam is deployed from the catheter. The device is typicallydelivered and deployed in the treatment region in a time frame of 5seconds to 30 minutes. More than one device may be required and/orchosen to achieve complete vessel occlusion.

In an embodiment, the device is composed of a polyurethane SMP. Incertain embodiments, the polymer is selected from N,N,N′,N′-Tetrakis(2-hydroxypropyl) ethylenediamine (HPED); 2,2′,2″-nitrilotriethanol(TEA); 1,6-diisocyanatohexan (HDI); and trimethylhexamethylenediisocyanate (2,2,4- and 2,4,4-mixture) (TMHDI).

In an embodiment, the occlusion of a blood vessel occurs as a result offlow stagnation of the blood caused by the morphology of the device. Theocclusion also occurs as a result of the tissue injury response of theendothelium of the vessel to the implantation of the device and theexposure of tissue factor binding sites.

In certain embodiments, the occlusion occurs as a result ofrecirculation zones within the blood flow caused by the morphology ofthe implant. In other embodiments, the occlusion occurs as a result ofplatelet aggregation and activation throughout the volume of the device.

During in vitro blood flow studies, complete occlusion of the foamdevice was observed at 270 seconds. Complete occlusion was evidenced byflow diverting through a pressure relief valve. At this point, thepressure within the vein model created by thrombus formation exceededthe pressure relief valve setting and flow was diverted through thebypass pathway. Results show blood is penetrating throughout the entirevolume of the foam device, demonstrating the effectiveness of foam cellreticulation in creating interconnected pathways along the length of thedevice. After 30 seconds of blood perfusion, each cross section of thefoam consisted of primarily erythrocytes enmeshed in loose, interspersedfibrin. At 270 sec, approximately 50% of the proximal section of foamconsisted of dense fibrin, which likely contributed to the completevessel occlusion which occurred at this time point.

An embodiment is directed to a delivery mechanism which delivers theembolic device to an area needing treatment. In certain embodiments, thedelivery vehicle is a catheter, expanding balloon catheter, or aguidewire. When the delivery vehicle is a guidewire, in some embodimentsthe device is crimped over the core wire to provide sufficient frictionbetween the implant and core wire to allow retraction and advancement ofthe device until it is fully expanded in the lumen of the treatmentvessel. The core wire is selected from stainless steel, nitinol, steelalloy, polypropylene, polytetrafluoroethylene, or nylon wire, or acombination of these materials comprising a braided wire or coil. Insome embodiments, the core wire is between 0.0005 and 0.050 inches indiameter.

An embodiment provides a minimally invasive approach to achieve completeocclusion of blood vessels and prevent recurrence through the use ofnitinol anchors on the proximal and distal ends of a polyurethane SMPfoam. While the SMP foam encourages rapid hemostasis and healing, thedevice anchors ensure the foam remains in the treated vessel, minimizingthe risk of embolization downstream of the target vessel and devicemigration.

Material modifications such as plasma surface treatments, addingradiopaque fillers, and heat treating can be employed to minimize thetime to hemostasis, optimize the design and dimensions of the device,ensure each component possesses adequate mechanical strength to preventdevice fracture and dislocation from the target region, and to evaluatethe deliverability, efficacy, and visualization of the device, viaultrasonography or X-ray in an in vitro model of a human great saphenousvein (GSV).

An embodiment uses polyurethane SMP foam that is actuated at 37° C.(although other embodiments actuate at 36, 38, 39° C. or more), whichmeans no external heating source is required to expand the foams afterimplantation. However, another embodiment has a higher transitiontemperature that requires the device to be actively heated via, forexample, heated saline injection, radiofrequency heating, and/or laserheating to initiate expansion.

In an embodiment, the SMP vessel occlusion device is delivered usingminimally invasive endovascular techniques in order to selectivelyocclude regions of vasculature where undesired persistent blood flow maycause complications. A SMP foam is crimped over a core wire and attachedto a pusher system that allows the device to be navigated through thelumen of the catheter in order to reach the target site. Upon contactwith blood, the device expands and resumes its pre-crimped geometry.This allows for a window of time between zero to thirty minutes for thedelivery of the device to the treatment region. The foam expands uponexiting the catheter in order to fill the entire cross-section of thevessel. Once the foam completely expands, the pusher system can beretracted due to less friction between the foam and the core wire. Thisallows the pusher system and catheter to be removed while leaving thefoam implant in place. In an embodiment thrombosis occurs within theentire volume of foam within 0 to 90 minutes. The porous morphology ofthe implant initiates the clotting cascade by creating manyrecirculation zones and flow stagnation in the blood stream. Theclotting cascade is further stimulated by the expansion of the foamimplant which damages the endothelium and exposes tissue factor bindingsites. The expansion of the foam implant also triggers the foreign bodyresponse.

An embodiment uses a pure foam device whereby a SMP foam is synthesized,reticulated, cut to the desired geometry using biopsy punches,mechanically conditioned using a heated stent crimper, dried in afreeze-dryer, and then crimped to its deliverable geometry. This allowsthe foam device to be delivered to the target region via an introducer,catheter, and guidewire.

Another embodiment is directed towards areas of high flow including, butnot limited to, arterial flow. An internal elastic wire that optionallyruns through the middle of the foam is laser welded or epoxied to theexternal surface of the distal anchor. The proximal anchor is attachedin the same manner as the distal anchor.

Another embodiment contains anchors proximal, distal, or in bothlocations relative to the SMP foam. The anchors contain a longitudinalmember that is inserted centrally through a cylinder of SMP foam, whichis then coated with a neat polymer solution consisting of a combinationof N,N,N′,N′-Tetrakis(2-hydroxypropyl)ethylenediamine (HPED),2,2′,2″-nitrilotriethanol (TEA), 1,6-diisocyanatohexan (HDI), andtrimethylhexamethylene diisocyanate (2,2,4- and 2,4,4-mixture) (TMHDI)that acts as an epoxy attaching the SMP foam to the coil backbone. Theneat polymer solution may itself constitute a SMP (which may be foams ormay not be foamed).

Foam and Device Synthesis

Various versions of SMP foam have been fabricated. For example, oneversion contains 100% hexamethylene diisocyanate (HDI) and anothercontains a mixture of HDI and trimethylhexamethylene diisocyanate(2,2,4- and 2,4,4-mixture) (TMHDI) for the isocyanate monomer in thepolyurethane reaction. The less hydrophobic 100% HDI foam was madespecifically for vessel implantation to allow for immediateself-actuation of the VOD in vivo without the need for external heating.The foam actuates at body temperature after exposure to moisture in theblood which causes a drop in the material's transition temperature. Bothfoams were reticulated and chemically post-processed in the same mannerAside from their different hydrophobicities, these two foams share verysimilar mechanical properties and shape memory characteristics. Duringthe foaming process, the material is constrained by the side walls ofthe container and unconstrained from above as it rises. Due to theseconditions and their ultra-low densities, the foams may have ananisotropic morphology.

In greater detail and as detailed in Landsman et al., Design andVerification of a Shape Memory Polymer Peripheral Occlusion Device,Journal of the Mechanical Behavior of Biomedical Materials 63 (2016):195-206, foams were fabricated as follows (although other methods may beused). Isocyanate (NCO) prepolymers were synthesized with appropriatemolar ratios of N,N,N′,N′-Tetrakis(2-hydroxypropyl)ethylenediamine(HPED, 99%; Sigma-Aldrich Inc., St. Louis, Mo.), triethanolamine (TEA,98%; Sigma-Aldrich Inc.), and hexamethylene diisocyanate (HDI, TCIAmerica Inc., Portland, Oreg.). The prepolymers were reacted for 2 dayswith a temperature ramp from room temperature to 50° C. at a rate of 20°C./hr, held isothermally at 50° C. for 16 hours, and passively allowedto cool back to room temperature. A hydroxyl (OH) mixture was blendedwith the remaining molar equivalents of HPED and TEA. This mixture alsocontained deionized (DI) water (>17 M Ω cm purity; Millipore waterpurifier system; Millipore Inc.), and catalysts (T-131 and BL-22, AirProducts and Chemicals, Inc., Allentown, Pa.). During the foaming step,the NCO prepolymer and the OH mixture were combined in a foaming cupalong with surfactants (DC 198 and DC 5943, Air Products and Chemicals,Inc., Allentown, Pa.) and the physical blowing agent, Enovate 245fa(Honeywell International, Inc., Morristown, N.J.). This solution wasmixed in a FlackTek Speedmixer (FlackTek, Inc., Landrum, S.C.) andpoured into a bucket to form a foam. The foam was cured at 60° C. for 5minutes before passively cooling to room temperature for furtherprocessing. Various foam formulations and pore sizes were fabricated tocreate foams with differing crosslink densities, glass transitiontemperatures (Tg), rate of moisture plasticization, and subsequent foamexpansion rates. Foam formulations are denoted as H20-H60, where thenumerical value appearing after “H” corresponds to the ratio of HPED toTEA equivalents in the polymer premix. Both foam formulation and poresize were used to control the expansion rate of the foams and theresultant working time to enable catheter delivery.

After fabrication, foams were cut into blocks 2 cm thick, 7 cm long, and6 cm wide. These blocks were then reticulated using the same methoddescribed previously (Rodriguez, J.; Miller, M.; Boyle, A.; Horn, J.;Yang, C.; Wilson, T.; Ortega, J.; Small, W.; Nash, L.; Skoog, H.; andMaitland, D., Reticulation of low density SMP foam with an in vivodemonstration of vascular occlusion, Journal of the Mechanical Behaviorof Biomedical Materials 40 (2014): 102-114). In short, the foams werepenetrated by a floating pin array while subjected to low amplitude,high frequency perturbations, which allowed the creation of pinholes inthe foam pore membranes. These pinholes create interconnected poresthroughout the foam which allow blood flow and eventual connectivetissue deposition to penetrate throughout the entire device.

After reticulation, the foams were cut with disposable biopsy punches(Sklar Surgical Instruments, West Chester, Pa., USA) for three differentdevice sizes-6, 8, and 12 mm. These device sizes were used to enabledelivery through 4, 5, and 6Fr catheters, respectively, and the abilityto treat vessels with diameters between approximately 2-11 mm After thefoams were cut into their final geometry, they were cleaned to removeany plasticizers and unreacted monomers from the foams. Each cleaningcycle lasted 15 minutes and was performed under sonication in a 40° C.water bath. The first two cleaning cycles consisted of submerging thefoams in 99% isopropyl alcohol (VWR, Radnor, Pa.). Then the foams wererinsed with reverse osmosis (RO) water before being cleaned in fourcycles of Contrad 70 liquid detergent (Decon Labs, King of Prussia,Pa.). Each foam was then rinsed with RO water until no Contrad 70residue was evident. Finally, the foams were cleaned for two cycles inRO water. After cleaning, the damp foams were frozen in a −20° C.freezer for 12 hours before freeze-drying in a FreeZone Freeze Dryer(Labconco, Kansas City, Mo.) for 24 hours.

Due to the low radial force of the SMP foams, a coil anchor isincorporated into some embodiments of the peripheral embolic device(PED) to enable implantation in both arteries and veins with minimalrisk of device migration. To fabricate the coil anchors used for invitro device verification tests, 0.018″ diameter 90/10% platinum/iridiumcoils with an inner diameter of 0.010″ were threaded over 0.005″,0.006″, and 0.008″ diameter superelastic nitinol wire for the 6, 8, and12 mm PED devices, respectively. The coils were then wrapped around astainless steel mandrel that had been machined to each device diameterand shape-set in a 550° C. furnace for 15 minutes. After 15 minutes, themandrels were immediately quenched in room temperature water to set thefinal shape of the coil. The coils were removed from the mandrel and astraight section of the coil was manually threaded through the center ofthe foam before crimping. While immediately above the platinum/iridiumcoil includes a channel to receive the nitinol wire in other embodimentsthe platinum/iridium coil and nitinol wire are merely coupled to eachother.

Mechanical Characterization of the Foams

Mechanical testing of SMP foams was performed in compression modeaccording to ASTM D1621-10 Standard Test Method for CompressiveProperties of Rigid Cellular Plastics using the Instron load frame witha 500 N load cell at ambient laboratory temperatures 23±2° C.Cylindrical samples 25.4 mm in diameter by 25.4 mm tall of both thenon-reticulated and reticulated (chemically etched or not etched) foamswere prepared. These samples were frozen in a −80° C. freezer overnightand subsequently lyophilized for 24 hours prior to mechanical testing.To assess the effects of pin mass, uni-axial versus tri-axialreticulation, and chemical etching, nine different reticulation schemes(including a non-reticulated control) were investigated as outlined inTable 1. Five (5) samples were tested for each version. At least some ofthe reticulation schemes and methods addressed herein are furtheraddressed in greater detail in Rodriguez, J.; Miller, M.; Boyle, A.;Horn, J.; Yang, C.; Wilson, T.; Ortega, J.; Small, W.; Nash, L.; Skoog,H.; and Maitland, D., Reticulation of low density SMP foam with an invivo demonstration of vascular occlusion, Journal of the MechanicalBehavior of Biomedical Materials 40 (2014): 102-114.

TABLE 1 Number of Chemical samples Nitinol pin mass etch testedUni-axial 1 g axial No 5 1 g axial Yes 5 2 g axial No 5 2 g axial Yes 5Tri-axial 1 g axial, 1 g trans-axial No 5 1 g axial, 1 g trans-axial Yes5 2 g axial, 1 g trans-axial No 5 2 g axial, 1 g trans-axial Yes 5Non-reticulated control Not applicable No 5

In Vivo Vascular Occlusion Assessment

Uni-axial and tri-axial reticulated SMP foam samples were cut into 20-30mm long cylindrical samples using a 10 mm diameter biopsy punch. Thesamples were pre-conditioned by radially compressing to 1 mm diameterusing a SC250 stent crimper (Machine Solutions Inc., Flagstaff, Ariz.)at 97° C. and heated to expand to their original shape. The SMP foamcylinders were then chemically etched, rinsed, and cleaned. The sampleswere dried in vacuum and stored in an air-tight container withdesiccant. The cylindrical samples were cut to 8 mm diameter usingfine-tip scissors and 10 mm long using a razor blade. Samples were thenradially compressed to the minimum diameter of approximately 1 mm usingthe stent crimper at 97° C., cooled under compression to maintain thecompressed shape, and stored in an air-tight container with desiccantuntil implantation in vivo.

Six (6) devices (3 uni-axial and 3 tri-axial reticulated using 1 g pinsand etching) were successfully deployed into multiple hind limb vesselsof a three month old, 25 kg pig. Angiography performed prior toimplantation of the VODs indicated the diameters of the vessels were onaverage 2.6 mm in diameter, which was smaller than the 8-mm diameter ofthe uncompressed VODs; therefore, the devices were able to expand toapproximately 33% of their original diameter. A 5F catheter, 0.055″inner diameter, was navigated to the implant site using a 0.035″guidewire. The compressed foam VOD was submerged in room temperaturesaline for 2-5 min and then submerged in 32° C. saline for 3-5 s. Thedevice was placed inside the catheter for 5 min to allow the foam tobegin expanding and then pushed out of the catheter using the 0.035″guidewire (FIGS. 1A to 1C). This procedure resulted in expansion of thefoam immediately as it emerged out of the catheter as shown in apreliminary benchtop in vitro demonstration (FIGS. 1D to 1F). Contrastenhanced fluoroscopy was used to determine when the device had beendeployed, by observing the location of the guidewire and if possible, alack of contrast agent in the vessel. After delivery into the vessel,the device expanded to its primary shape and subsequently blocked thevessel. The vessel occlusion time was defined as the time after devicedelivery until injected contrast agent ceased to flow through or pastthe device; at that point clotting is likely to have occurred. Vesselocclusion time was determined via iodinated contrast injectionsvisualized with angiography 45 s after deployment and then at 30 sintervals thereafter.

In Vivo Vascular Occlusion

The uni-axial reticulated foam had an average occlusion time of 90±11 sand the tri-axial reticulated foam had an average occlusion time of128±77 s. On average, the uni-axial reticulated foam induced fasterocclusion that the tri-axial reticulated foam. This result is notunexpected since blood flow is likely impeded more by the lessreticulated foam, potentially resulting in more rapid clotting due toincreased flow stagnation and surface area. Due to the great differencein occlusion time exhibited by the tri-axial foam relative to theuni-axial foam, the effects of the extent of reticulation on occlusiontime are still being investigated.

FIG. 1 shows a schematic diagram of endovascular deployment of andembodiment of the SMP foam vascular occlusion device (VOD): (A) thedevice is pushed near the 5F catheter tip (distal end of the catheter)by the guidewire 101, (B) the guidewire pushes the self-actuating device103 out of the catheter 102, and (C) the deployed device fills thevessel lumen 104. FIGS. 1(D-F) show in vitro demonstration of anembodiment of VOD deployment showing immediate expansion of the VOD foam102′ in 37° C. (body temperature) water in a silicone tube (3.5 mm innerdiameter) after deployment from catheter 103′.

FIG. 2 shows a bulk foam device navigated through the catheter 202 (A),distal tip of the device exposed to circulating flow (B), distal tip offoam 203 completely expanded and apposed to vessel wall (C), unsheathingthe device (D), the device completely deployed (E), and subsequentdelivery of a second device 205 (F).

FIG. 3 shows a device embodiment that consists of a shape memory polymerfoam 303 plug with a leading edge coil anchor 306 (distal) and aproximal radiopaque marker 307.

FIG. 4 shows a crimped (A) and expanded (B) device embodiment whichconsists of a shape memory polymer foam plug 403 with a distal coilanchor 406 that extends through the core of the device.

FIG. 5 shows a device embodiment that consists of a shape memory polymerfoam 503 plug with a proximal 506 and distal 507 coil anchor. In anembodiment the anchors include radiopaque markers 508 and/or 509.

FIG. 6 shows a device embodiment that consists of a shape memory polymerfoam plug 603 with proximal and distal flower-shaped anchors 606, 607cut from a monolithic tube of nitinol.

FIG. 7 shows thermomechanical analysis of various foam formulations usedin device fabrication, which demonstrate the tunability of the glasstransition temperature of the device.

In greater detail, differential scanning calorimetry (DSC) was used toassess the ability to control the activation temperature of embodiments,which corresponds to the Tg of the materials of the embodiments. It iscritical that the actuation temperature of these devices is greater thanthe temperature at which they are stored to prevent premature expansionof the foams. The Tg for all foam formulations ranged between 49 and 70°C. FIG. 7 shows representative thermograms for each foam compositionused, where H20-H60 correspond to foam compositions with 20-60% molarequivalents of HPED. The thermograms demonstrate a single transitionwith no indication of a secondary transition, as well as a nearly linearrelationship between increasing Tg as the ratio of HPED to TEA alsoincreases. The average Tg ranged from H20 (49.85° C.) to H60 (69.44°C.).

Foam Composition Average Tg (° C.) Standard Deviation H20 49.84 0.15 H3053.33 0.58 H40 58.83 0.28 H50 62.49 0.26 H60 69.44 0.39

Devices fabricated using H20 and H30 formulations expanded too rapidlyto allow delivery of devices via catheter. For this reason, someembodiments include H40, H50, and H60 foams. There is a general trend ofdecreasing expansion rate, within the first three minutes of submersionin 37° C. water, as the crosslink density of the foam increases (higherHPED content). The first three minutes of exposure to aqueousenvironments is critical in embodiments designed to be delivered withinthree minutes after first contacting blood or saline. Pore size also hada dramatic effect on expansion rate where expansion rate decreased asthe pore size decreased due to increased foam density delaying waterdiffusion into the foam matrix. However, regardless of pore size andfoam composition, all samples experienced 100% shape recovery in lessthan 20 minutes.

FIG. 8 shows a crimped and expanded image of a foam-over-coil embodimentof the embolization device where a coil 806 is placed centrally throughthe core of a cylindrical piece of foam 803.

FIG. 9 shows an illustration of the foam-over-coil embodiment of theembolization device where a coil 906 is placed centrally through thecore of a cylindrical piece of foam 903 and there is a distal section ofexposed coil without foam. An embodiment includes radiopaque markers 908and/or 909.

FIG. 10 shows an illustration of the foam-over-coil embodiment of theembolization device where a coil 1006 is placed centrally through thecore of a cylindrical piece of foam 1003 and the diameter of coilgradual increases towards one end of the device similar to a spiral. Anembodiment includes radiopaque markers 1008 and/or 1009.

As described herein, through the use of DSC, embodiments allow precisecontrol of the actuation temperature of SMP foams by altering the ratioof HPED to TEA. The increase in Tg as the amount of HPED increases is aresult of the increased crosslink density associated with additionalHPED and the steric hindrance provided by the molecular structure ofHPED which limits chain mobility. The ability to control the Tg of SMPfoam devices is highly useful for controlling the actuation rate of thedevice when exposed to circulating blood. This provides a simple meansof altering the expansion kinetics of the foam to satisfy the uniquespecifications required by clinicians for different device indications.

Since the activation of SMPs is entropy-driven and body temperature islower than the Tg of each foam formulation, some embodiments of thepolymers must experience plasticization in the blood or saline injectioninside the delivery catheter in order to depress the Tg sufficiently toinitiate expansion. Although the transition temperature of these foamsare significantly greater than 37° C., the Tg of the foams is depressedto approximately 10° C. when exposed to 100% humidity. This transitiontemperature depression is what allows the foams to expand in the 37° C.aqueous environment within the body. The expansion studies demonstratedthe ability to tune the working time of the proposed device, defined asthe point at which the expanded diameter of the foam is four times theinner diameter of the delivery catheter. By altering the ratio of HPEDto TEA during foam fabrication and the foam pore size, devices can befabricated with working times varying from one to five minutes.

An average burst pressure of human saphenous veins is approximately1,575 mm Hg. Based on this burst pressure and a PED 8 mm in diameter and2 cm long device, the radial force of the foams must not exceed 107N toprevent vessel rupture in the venous system. This maximum radial forceassumes a uniform distribution of radial force exerted along the lengthand circumference of the device. Based on this information, radial forcetests demonstrated that the SMP foams exert a radial force on the vesselwall that is drastically smaller than would be required for vesselrupture. This is also considering that the foams are oversized by 50% tothe inner diameter of the vessel, which is the common sizing practicewhen selecting an appropriately sized vascular plug. This testdemonstrated that the risk of rupturing the target vessel with thisdevice as a result of foam expansion is extremely low, regardless ofwhich foam formulation is used. The more likely device component tocause vessel perforation or rupture is the coil anchor. Although theradial force of the coil exceeds that of foam, it exerts nearly an orderof magnitude less force than commercially available vascular plugs usedfor peripheral occlusion, as well as less than 50% of the pressurerequired to rupture saphenous vein grafts and approximately 50% lesspressure than FDA-approved embolic plugs currently on the market. Themechanical forces exerted by the PED implicate that the risk of vesselrupture as a result of the coil anchor is low.

Device migration studies demonstrated that embodiments are at least asstable as Cook Nester® Coils. Although embodiments provided equal orsuperior resistance to undesired thromboembolism, device stiffnesstesting demonstrated that the embodiments are significantly less stiffthan current embolic plugs used on the market, such as the AVP II. Thereduction in stiffness and use of a coil anchor for stability ratherthan an expandable nitinol mesh, allows the PED embodiments to bedelivered to small, tortuous vessels that may not be accessible to otherembolic plugs due to the risk of catheter deflection and excessive forcerequired to advance the device.

Embodiments of the SMP foams provide sufficient echogenicity to enabledelivery using ultrasound guidance. The ability to deliver these devicesusing ultrasound guidance also allows for embodiments consistingentirely of SMP foam with no metallic components that can still bedelivered and visualized using endovascular techniques. Althoughdependent on the depth of the treatment vessel within the body,ultrasound imaging provides a means of delivering these devices withoutsubjecting the patient to any radiation or potential side effects of thecontrast injections required during fluoroscopy.

In vitro blood perfusion studies and the subsequent histologicalanalysis of SMP foam devices revealed that blood penetrated throughoutthe device. No foam sections appeared to be devoid of thrombusdeposition, and a dense fibrin mesh was clearly visible at proximal,middle, and distal locations of the device at the moment in whichcomplete vessel occlusion occurred. Complete occlusion was witnessedafter 270 seconds of blood perfusion through the device. The pressuresetting used in this experiment (450 mmHg) served as a rigorous test ofin vitro clotting of the device as flow would likely be diverted,thereby creating clinical occlusion, from the treatment vessel at muchlower pressures in vivo. Considering the absence of tissue factor VIIand any influence from the extrinsic clotting cascade on thrombusformation, complete occlusion in less than five minutes is a significantachievement; especially considering certain FDA-approved peripheralembolization devices may require more than 5 minutes to achieve vesselocclusion.

Embodiments discussed herein show the mechanical properties of the shapememory polymer PED device are safe and unlikely to cause vesselperforation or rupture. At the same time, these studies demonstratedthat the likelihood of device migration and undesired thromboembolism tobe minimal. Embodiments accomplished this while also demonstrating asignificant reduction in overall device stiffness compared tocommercially available vascular plugs, which allows embodiments to bedelivered to tortuous vessels that may not be accessible usingconventional embolic devices. Embodiments cause complete vesselocclusion and encourage rapid thrombus formation, and demonstrate easeof visualization of the PED using ultrasound and/or fluoroscopy and thelike.

FIG. 12(A) includes an embodiment similar to FIG. 3(A). For example, acoil (in its primary shape) has been deployed from a catheter. The SMPfoam has not yet been ejected or deployed from the catheter. In FIG.3(B) the SMP foam has been deployed from the catheter upstream of thecoil. In this embodiment the foam is deployed within a cage structure(“expanded delivery tube”). This tube may have splines or struts that,upon no longer being constrained by the catheter, open radially toproject force against the vessel walls (possibly helping spread apartwalls that have partially collapsed). The splines may be superelastic.The splines may include, for example, stainless steel or nitinol. Thefoam expands to its primary shape while still within (partially orcompletely) the struts of the cage structure.

If the physician determines the foam is improperly deployed, thephysician may withdraw the cage back into the catheter and in so doing,have the cage arms or splines collapse around the misplaced foam andwithdraw the foam into the catheter. In such a case the guidewire (usedto deploy the foam from the “expanded delivery tube” and ultimatelydeliver the device to the vessel) and the cage may be separate from oneanother. The guidewire and cage may be withdrawn simultaneously, or thecage may be withdrawn while the guidewire position is maintained priorto the guidewire withdrawing into the catheter.

As seen in FIG. 12(C), if the foam is properly placed the guidewire mayremain deployed (thereby keeping the foam deployed) while the cage iswithdrawn causing the cage to collapse within the catheter. This hasbegun to occur in FIG. 12(C) and is continuing in FIG. 12(D). As shownin FIG. 12(D), the foam remains coupled to the coil anchor (via a metalbackbone) and, if the foam moves downstream, the foam will move towardsthe coil anchor. In FIG. 12(D) the guidewire is clearly shown furtherdeployed (closer to anchor) than the cage.

As noted above, the guidewire may merely push against a proximal portionof a metal backbone (i.e., the guide wire is not fixedly coupled to thebackbone) that couples to the anchor or the guidewire. However, in otherembodiments the guide wire may have an electrolytic release from thebackbone and the like (e.g., guidewire couples to the backbone at a nodethat can be terminated via electrolytic process/reaction). The guidewiremay couple via threads whereby the guidewire and backbone havecomplementary threads for coupling to each other.

FIG. 12(E) shows the catheter, cage, and guidewire being withdrawn awayfrom the deployed anchor and foam (labeled “Implanted device”).

In an embodiment the cage frame may be a monolithic design fabricatedfrom a single, continuous material. For example, the struts may beformed from a single, continuous tube, where the struts are cut andpositioned from the tube. In some embodiments, the cage may have 2-30struts. The struts may have a free end (shown distal or downstream) anda fixed end where they couple to a portion of the tube that has not beencut. In other words, their distal ends may be free from each other whiletheir proximal ends all terminate at a band that is a portion of a tubefrom which the arms were formed.

The struts may be constructed of elastic, biocompatible materials havinga high strain recovery. In some embodiments, a shape memory alloy havinga strain recovery of 3% may be used (however other embodiments are notso limited and may include shape memory elements with strain recovery of4%, 6%, 8%, 10% or more). Materials that may be used include, but arenot limited to: shape memory alloys; titanium alloys, such as nitinol;copper-base alloys, such as Cu—Al—Ni; platinum alloys, such as Fe—Pt;chromium-cobalt alloys, such as Co—Cr—Mo; cadmium-base alloys, such asAg—Cd; shape memory polymers, such as urethane; and stainless steel. Thestruts may be comprised of combinations of materials; for example, theproximal segment may be nitinol, the intermediate segment may bestainless steel, and the distal segment may be Co—Cr—Mo.

To make the cage structure an embodiment entails cutting a plurality ofslots into an elastic tube. Cutting slots in a tube, wire, or rod maycreate the form of struts. For devices having continuous struts down thedevice frame, a single set of slots may be cut. The struts may be cut bya laser or other precision cutting device. The device cage frame may beshape set. Shape setting may involve creating a permanent shape for thedevice cage frame. For metal frames, shape setting may include moldingthe device frame to an expanded shape to which the device returns whenradial restrictions are removed, such as through deployment from a tube.The device frame shaping may include forming a device frame and heattreating the device frame. Device formation may be performed by settingthe tube in a mold structure and compressing the tube so that the strutsexpand into a preconfigured shape. Spacers corresponding to desiredstructure length may be placed in the corresponding section of tube; forexample, a 10 mm spacer may be placed in a section of tube correspondinga proximal structure, where the desired proximal structure length is 10mm. An external frame tailored to the desired structure diameter may beplaced around the corresponding section of tube. The tube may becompressed axially until the lateral struts contact the external frameand/or the internal radial struts contact the spacer. The process may beapplied subsequently or concurrently to other sections of the deviceframe. After formation of the preconfigured shape, the device may beheat treated to create a permanent shape to which the device frame willreturn to once external restrictions are removed.

The following examples pertain to further embodiments.

Example 1 includes an embolic device, wherein the device is used tostably occlude the flow of blood within a vessel undergoing treatment.

Example 2 includes the embolic device of example 1, wherein the clotformation and stable occlusion occurs within 0-30 minutes afterdeployment of the device.

Example 3 includes the embolic device of example 1, wherein the deviceis delivered and deployed in the treatment region in a time frame of 5seconds to 30 minutes.

Example 4 includes the embolic device of example 1, wherein the deviceis composed of a polyurethane SMP.

However, other embodiments may use a hydrogel or like in place of theSMP foam.

Example 5 includes the embolic device of example 4, wherein the polymeris fabricated using a combination of hexamethylene diisocyanate (HDI),trimethylhexamethylene diisocyanate (2,2,4- and 2,4,4-mixture) (TMHDI)N,N,N′,N′-Tetrakis(2-hydroxypropyl)ethylenediamine (HPED), and2,2′,2″-nitrilotriethanol (TEA).

Example 6 includes the embolic device of example 1, wherein theocclusion occurs as a result of flow stagnation of the blood caused bythe morphology of the device.

Example 7 includes the embolic device of example 1, wherein theocclusion occurs as a result of the tissue injury response of theendothelium of the vessel to device implantation and the exposure oftissue factor binding sites.

Example 8 includes the embolic device of example 1, wherein theocclusion occurs as a result of recirculation zones within the bloodflow caused by the morphology of the implant.

Example 9 includes the embolic device of example 1, wherein theocclusion occurs as a result of platelet aggregation and activationthroughout the volume of the device.

Example 10 includes the embolic device of example 1, wherein the deviceis made from a shape memory foam.

Example 11 includes the embolic device of example 1, further comprisingan anchor that holds the device in place within the blood vessel.

Example 12 includes the embolic device of example 11, wherein the anchoris placed proximal, distal, or at both locations relative to the device.

Example 13 includes the embolic device of example 11, wherein the anchorcomprises nitinol, platinum, stainless steel, polycarbonate, or acombination of these materials.

Example 14 includes a delivery mechanism, wherein the delivery mechanismdelivers the embolic device of example 1 to an area needing treatment,and remains at the location until the embolic device has expanded tocreate an occlusion.

Example 15 includes the delivery mechanism of example 14, wherein thedelivery mechanism is a catheter, expanding balloon catheter, or aguidewire.

Example 16 includes the delivery mechanism of example 14, wherein thedevice is crimped over the core wire to provide sufficient frictionbetween the implant and core wire to allow retraction and advancement ofthe device until it is fully expanded in the lumen of the treatmentvessel.

Example 17 includes the delivery mechanism of example 14, wherein thecore wire is a stainless steel, nitinol, steel alloy, polypropylene,polytetrafluoroethylene, or nylon wire, or a combination of thesematerials comprising a braided wire or coil.

Example 18 includes the delivery mechanism of example 14, wherein thecore wire is between 0.0005 and 0.050 inches in diameter.

Example 19 includes the device of example 5 wherein the foam includesradiopaque fillers, such as iodine, tungsten, platinum, barium sulphate,or any combination of these compounds.

Example 20 includes the device of example 5 wherein the morphology andsurface chemistry of the device causes fibrin deposition and plateletaggregation in less than 180 seconds.

Example 21 includes the anchor of example 12 wherein the anchor geometrycomprises a helix, spiral, or a helix with gradually increasingdiameters over the length of the device.

Example 22 includes the anchor of example 12 wherein the anchorcomprises a cylindrical tube that is cut such that it contains aplurality of struts that may extend outward from the original cylindergeometry.

Example 23 includes the device of example 4 wherein the device ismodified such that interconnected pathways are created through the SMP.

Example 1a includes a system comprising: an outer conduit havingproximal and distal ends; a shape memory polymer (SMP) foam havingproximal and distal ends and that transitions from a secondary shape toa primary shape when the SMP foam is heated above its glass transitiontemperature (Tg); a metal backbone including: (a)(i) a first portionthat extends from the SMP foam proximal end to the SMP foam distal endand which is generally covered by the SMP foam, and (a)(ii) a distalportion that extends distally from the SMP foam distal end and which isnot covered by the SMP foam; wherein: (b)(i) SMP foam and the metalbackbone are both included within the outer conduit adjacent to theouter conduit distal end; (b)(ii) the metal backbone distal portiontransitions from a secondary shape that is uncoiled to a primary shapethat is coiled; and (b)(iii) the metal backbone distal portion is in themetal backbone distal portion secondary shape and is located between theSMP foam distal end and the distal end of the outer conduit.

For instance, the outer conduit may include an introducer sheath orlumen that fits within a catheter or some other lumen. In an embodimentthe system is delivered to the end user in a contained package thatincludes the SMP foam already “loaded” within the introducer sheath andnear a distal end of the sheath so the SMP foam can be deployed from thesheath with minimal distance to traverse. In this case, the “distal” endis the end of the device furthest from the physician when the physicianis deploying the device. The primary shape of the SMP foam may be anexpanded cylinder such as the cylinder shown in the post-expansiondiagram of FIG. 3. The primary shape of the metal backbone distalportion may be a coil as shown in FIG. 3. Further, the Tg may depressdue to plasticization.

For instance, in FIG. 3 the metal backbone includes a portion (e.g.,portion 310) that extends from the SMP foam proximal end to the SMP foamdistal end and which is generally covered by the SMP foam 303. The metalbackbone may also include a portion 311 that extends distally from theSMP foam distal end 312 and which is not covered by the SMP foam.

For instance, the metal backbone distal portion transitions from asecondary shape that is uncoiled. FIG. 11 shows the secondary shape (see“Distal Pt/Ir Coil”) when the distal anchor is still within a catheter(or at least a portion of the anchor is still in the catheter) and hasnot yet been unconstrained such that it may return to its primary shapeof a coil.

As used herein Tg refers to the specific “glass transition temperature”whereas the “transition temperature” can refer to the Tg, the melttransition, or a crystallization temperature, among others. In anembodiment the SMP foam actuates at the Tg but may actuate at melttemperatures in other embodiments.

Another version of Example 1a includes a system comprising: an outerconduit having proximal and distal ends; a shape memory polymer (SMP)foam having proximal and distal ends and that transitions from asecondary shape to a primary shape when the SMP foam is heated above itstransition temperature; a metal backbone including: (a)(i) a firstportion that extends from the SMP foam proximal end to the SMP foamdistal end and which is generally covered by the SMP foam, and (a)(ii) adistal portion that extends distally from the SMP foam distal end andwhich is not covered by the SMP foam; wherein: (b)(i) SMP foam and themetal backbone are both included within the outer conduit adjacent tothe outer conduit distal end; (b)(ii) the metal backbone distal portiontransitions from a secondary shape that is uncoiled to a primary shapethat is coiled; and (b)(iii) the metal backbone distal portion is in themetal backbone distal portion secondary shape and is located between theSMP foam distal end and the distal end of the outer conduit.

In an embodiment the transition temperature equals the Tg for the SMPfoam.

Example 2a includes the system of example 1, wherein the SMP foam is apolyurethane SMP foam that includes N,N,N′,N′-tetrakis (2-hydroxypropyl)ethylenediamine (HPED), triethanolamine (TEA), and hexamethylenediisocyanate (HDI).

For instance, aside from the HDI the ratio of HPED to TEA may be used totailor the expansion rate. Expansion rates may be short (e.g., 1, 3, 5,7, 9 min) or longer (e.g., 20, 25, 30 min or longer). Embodiments mayinclude, for example, a range of 20 molar percent HPED to TEA all theway up to 80 molar percent HPED to TEA. Thus, embodiments may haveratios of moles of HPED to TEA of 0.2-0.8. However, other embodiments gooutside those bounds.

Other embodiments may include wherein the SMP foam includesN,N,N′,N′-tetrakis (2-hydroxypropyl) ethylenediamine (HPED),triethanolamine (TEA), and trimethylhexamethylenediamine (TMHDI) withHPED contributing a higher molar ratio of hydroxyl groups than TEA.

Other embodiments may include wherein the SMP foam includesN,N,N′,N′-tetrakis (2-hydroxypropyl) ethylenediamine (HPED), Glycerol,pentanediol, and hexamethylene diisocyanate (HDI).

Example 3a includes the system of example 2 wherein the metal backbonedistal portion includes an outer metal portion, including a channel, andan inner metal portion included within the channel.

For instance, see above for a description of how platinum/iridium coilswere threaded over superelastic nitinol wire. For instance, see innermetal portion 322 within outer metal portion 323 of FIG. 3.

Example 4a includes the system of example 3, wherein: the metal backbonefirst portion also includes the inner metal portion but does not includethe outer metal portion; and the inner metal portion is monolithic andextends from the SMP foam proximal end, to and through the SMP foamdistal end, and into the channel of the outer metal portion distal tothe SMP foam.

For instance, the inner metal portion may be a long monolithic (formedof one piece without seams or welds) wire that extends through the foam(area 310) and into the channel of the outer metal portion (area 311)while the outer metal portion may be restricted to area 311. As shown inFIG. 11, the outer metal portion may include platinum or iridium toprovide radioopacity, which may be lacking for the inner metal portion(which may include, for example, nitinol) and foam.

This may be true for the embodiments of FIGS. 9 and/or 10 as well. Forexample, the portions not covered by foam may include the outer metalportion over the inner metal portion and the parts that are covered byfoam may only include the inner metal portion.

Also, when delivering an embodiment under ultrasound, both the SMP andplatinum coil anchor provide sufficient echogenicity to allowvisualization. Significant acoustic shadowing indicative of anacoustically dense material was witnessed, providing further evidencethat the embodiment is likely to cause rapid occlusion upon expansion invivo. This shadowing is the same phenomenon used by physicians toidentify dense, calcified lesions within arteries with intravascularultrasound (IVUS).

Example 5a includes the system of example 4, wherein at least a portionof the outer metal portion is more radiopaque than both the inner metalportion and the SMP foam.

Example 6a includes the system of example 5, wherein the inner metalportion is superelastic.

For instance, the inner metal portion may include nitinol.Superelasticity may also be referred to pseudoelasticity. As usedherein, it is a property unique to shape memory alloys where they canreversibly deform to strains as high as 10%. This deformationcharacteristic does not require a change in temperature (like the shapememory effect), but the material needs to be above the transformationtemperature to have superelasticity.

Example 7a includes the system of example 6, wherein: the SMP foamincludes a proximal portion that includes the proximal end of the SMPfoam and a distal portion that includes the distal end of the SMP foam;and one of the proximal and distal portions of the SMP foam fixedlyadheres to the metal backbone first portion and another of the proximaland distal portions of the SMP foam slideably couples to the metalbackbone first portion.

For instance, in FIG. 3 the SMP foam may be epoxied or otherwise adheredto backbone portion 310 at areas 313 and/or 314 and/or 315. Adhering thefoam at only one of the locations allows the foam to travel along thebackbone while expanding radially. Thus, in an embodiment the foamslightly shrinks linearly when expanding radially. Further, adhering thefoam at some location helps ensure the foam stays coupled to the anchorif, for example, a user opts to deploy the system such that the foam islocated downstream of the anchor.

Example 8a includes the system of example 7, wherein the SMP foam andthe metal backbone distal portion are oriented with respect to eachother and with respect to the outer conduit so the metal backbone distalportion deploys from the distal end of the outer conduit before the SMPfoam deploys from the distal end of the outer conduit.

For instance, in FIG. 3 the system is deployed from catheter 318 in thedistal direction 316 into or towards downstream blood pressure (i.e.,blood is moving in direction 317). In this case, the anchor 306 is ableto form the “leading edge” and points “downstream” whereas foam 303 islocated upstream of the anchor. This is beneficial in that anydownstream movement of foam 303 will actually push the foam towards theanchor and in so doing will cause the coil to produce greater radialforce 319, thereby driving the coil further into the vessel therebystabilizing the system and preventing the system from moving downstream.This added force into the endothelial lining of the vessel may furtherillicit a healing response described herein.

To ensure embodiments had a limited risk of migrating downstream andcausing unintended thrombosis, studies were conducted in which themaximum flow rate was determined for each embodiment size for comparisonto a conventional embolic coil, Cook Medical's Nester® Embolic Coil.Results showed the embodiments can withstand equivalent or higher flowrates than Nester® coils. This analysis was also performed with only oneNester® coil within the mock vein, whereas at least three coils aretypically implanted to achieve complete vessel occlusion in the clinic.If three coils were implanted into the test section, the pressure dropacross the device mass would drastically increase, and the maximum flowrate for these coils would likely decrease further.

Example 9a includes the system of example 8 comprising a proximal metalportion that is: (c)(i) coupled to the inner metal portion, (c)(ii)located proximal to the SMP foam, (c)(iii) included within the outerconduit, and (c)(iv) is more radiopaque than both the inner metalportion and the SMP foam.

For instance, one such proximal metal portion may include node 307 ofFIG. 3. Also see the “proximal marker band” of FIG. 11. In such a case,the physician can determine the location of the foam based on the“ghost” space between the band and the anchor (see “foam” of FIG. 11).

Example 10a includes the system of example 8, wherein at least one ofthe proximal metal portion and metal backbone includes an outer diameterthat is at least 50% of an inner diameter of the outer conduit.

For example, the “Proximal marker band” of FIG. 11 may comprise adiameter 60, 70, 80, or 90% of the catheter or outer conduit withinwhich it resides. Therefore a guide wire or pushing rod cannot easilyslip between the marker band and the catheter wall. As a result, theguide wire or pushing rod easily couples to the device and canefficiently push the device out of the catheter.

Example 11a includes the system of example 8, wherein: the metalbackbone first portion is aligned along an axis; and the metal backbonedistal portion, in its primary shape, provides a radial force that isgenerally orthogonal to the axis and is greater than another radialforce exerted by the SMP foam.

Such an axis is axis 320 of FIG. 3 and such a radial force of the anchoris force 319 and the radial force of the foam is force 321.

Radial force tests demonstrated that the radial force of foam devicesconsistently increased as the device diameter increases. The results forthe radial force tests are summarized below.

Foam Device Diameter Vessel Diameter Radial Force Composition (mm) (mm)(N) H40 4 2.7 0.08 ± 0.03 6 4.0 0.16 ± 0.03 8 5.3 0.24 ± 0.05 10 6.70.30 ± 0.05 H50 4 2.7 0.13 ± 0.07 6 4.0 0.17 ± 0.04 8 5.3 0.21 ± 0.04 106.7 0.25 ± 0.03 H60 4 2.7 0.20 ± 0.04 6 4.0 0.29 ± 0.07 8 5.3 0.38 ±0.05 10 6.7 0.36 ± 0.09

These tests show the radial force of SMP foams with varied foamchemistries (H40, H50, H60). A pore size of 0.5±0.1 mm was chosen foranalysis of all chemistries after testing the radial force of foamsamples with 0.5, 1, and 1.5 mm pore sizes, which revealed that foamswith the smallest pore size exert the greatest radial force due toincreased foam density. Constrained recovery tests demonstrated that themaximum force exerted on the vessel walls by foam expansion when thefoam is 50% oversized to the target vessel is significantly lower thanthe 107N of force required to rupture autologous veins commonly used inbypass procedures, if we assume a uniform cylindrical surface area ofthe foam.

The radial stiffness of each different sized anchor was compared to thestiffness of two conventional vascular plugs. During radial forcetesting to determine device stiffness values, the 8 mm devices exertedan average maximum radial force of 4.0N, while the AMPLATZER™ VascularPlugs (AVP II, St. Jude Medical, St. Paul, Minn.) exerted an averagemaximum radial force of 15.8N when oversized by 50% to the targetvessel. Microscopic imaging of the 8 mm PED anchor coil revealed thatapproximately 30% of the coil surface area is in contact with the vesselendothelium, which corresponds to 0.43 cm2 of surface area. Given theestimated surface area of coils in contact with the vessel lumen, thePED anchor would exert a pressure of approximately 700 mmHg on thevessel endothelium-less than half the pressure required to cause rupturein an autologous vein graft. When a 16 mm AVP II was deployed within aflexible PVC tube with an inner diameter of 10 mm, it was estimated thatapproximately 0.85 cm2 of device surface area was in contact with theinner diameter of the tubing, resulting in a radial pressure ofapproximately 1,400 mmHg Given the proven safety and efficacy of the AVPII device that led to its FDA approval, and the markedly reduced radialforce and pressure exerted by the PED anchor, it is unlikely that thePED coil anchor would cause vessel rupture or perforation in vivo. Priorto verification tests, it was hypothesized that the coil anchor wouldaccount for the vast majority of the radial force exerted by the PED.Radial stiffness testing revealed that this was indeed the case, asdemonstrated by a maximum radial force of less than 0.5N for any foamstested.

Example 12a includes the system of example 8, wherein the outer conduitincludes an introducer sheath.

Example 13a includes the system of example 8, wherein: the metalbackbone first portion is aligned along an axis; and the SMP foam andthe metal backbone distal portion are oriented with respect to eachother so when upstream blood pressure forces the SMP foam towards themetal backbone distal portion the metal backbone distal portion, in itsprimary shape, presses radially outwards in a direction generallyorthogonal to the axis and in response to the upstream blood pressureforcing the SMP foam towards the metal backbone distal portion.

Example 14a includes the system of example 8 with the TEA contributing alower molar ratio of hydroxyl groups to the polyurethane SMP foam thanthe HPED.

Example 15a includes the system of example 8 with the TEA contributing ahigher molar ratio of hydroxyl groups to the polyurethane SMP foam thanthe HPED.

Example 16a includes the system of example 15, wherein the polyurethaneSMP foam includes a diisocyanate component consisting of the HDI and noother diisocyanate component.

For example, no TMHDI is used. This can be critical to promote rapidexpansion of the foam in scenarios concerning traumatic injury whereblood flow must be stopped quickly (e.g., less than 5 min or even lessthan 3 min).

Example 17a includes the system of example 8, wherein the outer metalportion includes at least one of platinum, palladium, tungsten, andiridium.

Example 18a includes the system of example 8 comprising an additionalouter metal portion proximal to the SMP foam and not covered by thefoam, wherein: the additional outer metal portion includes an additionalchannel; the inner metal portion extends to and through the SMP foamproximal end and into the additional channel; and the inner metalportion that extends to and through the SMP foam proximal end and intothe additional channel also transitions from a secondary shape that isuncoiled to a primary shape that is coiled.

For example, see FIG. 5. In such a case, the inner metal portion may bea single nitinol wire that extends throughout the length of the foam andinto platinum coatings (e.g., outer metal portions) on both ends of theinner metal portion wire. In such a case, no marker bands may be neededas the physician can determine the location of the foam based on the“ghost” space between the two anchors.

Example 19a includes the system of example 8, wherein the metal backbonedistal portion primary shape that is coiled includes a conically shapedcoil with a base of the conically shaped coil between the SMP foam and avertex of the conically shaped coil.

For instance, in FIG. 10 base 1024 may be ejected from the catheter orouter conduit after vertex 1025. In such an instance the base may belocated upstream of the vertex. Further, a “conically shaped coil” asused herein includes a frustoconical shape (the basal part of a solidcone or pyramid formed by cutting off the top by a plane generallyparallel to the base). Further, the coil of FIG. 3 may be conical withthe base closer to the foam than the vertex or where the vertex iscloser to the foam than the base. The same is true for either or both ofthe coils of FIG. 5 wherein either or both of the coils of FIG. 5 may beconical with the base closer to the foam than the vertex or where thevertex is closer to the foam than the base

Example 20a includes a method comprising: providing a system comprising:an outer conduit having proximal and distal ends; a shape memory polymer(SMP) foam having proximal and distal ends and that transitions from asecondary shape to a primary shape when the SMP foam is heated above itsglass transition temperature (Tg); a metal backbone including: (a)(i) afirst portion that extends from the SMP foam proximal end to the SMPfoam distal end and which is generally covered by the SMP foam, and(a)(ii) a distal portion that extends distally from the SMP foam distalend and which is not covered by the SMP foam; wherein: (b)(i) SMP foamand the metal backbone are both included within the outer conduitadjacent to the outer conduit distal end; (b)(ii) the metal backbonedistal portion transitions from a secondary shape that is uncoiled to aprimary shape that is coiled; and (b)(iii) the metal backbone distalportion is in the metal backbone distal portion secondary shape and islocated between the SMP foam distal end and the distal end of the outerconduit; advancing the system into a patient; deploying the metalbackbone distal end from the outer conduit distal end into a vessel ofthe patient; transitioning the metal backbone distal end from itssecondary shape to its primary shape; engaging the metal backbone distalend with a wall of the vessel in response to transitioning the metalbackbone distal end from its secondary shape to its primary shape;deploying the SMP foam from the outer conduit distal end into the vesselin response to deploying the metal backbone distal end from the outerconduit distal end; transitioning the SMP foam from its secondary shapeto its primary shape; engaging the SMP foam with the wall of the vesselin response to transitioning the SMP foam from its secondary shape toits primary shape; and occluding the vessel in response to engaging theSMP foam with the wall of the vessel.

Another version of Example 20a includes a method comprising: providing asystem comprising: an outer conduit having proximal and distal ends; ashape memory polymer (SMP) foam having proximal and distal ends and thattransitions from a secondary shape to a primary shape when the SMP foamis heated above its transition temperature; a metal backbone including:(a)(i) a first portion that extends from the SMP foam proximal end tothe SMP foam distal end and which is generally covered by the SMP foam,and (a)(ii) a distal portion that extends distally from the SMP foamdistal end and which is not covered by the SMP foam; wherein: (b)(i) SMPfoam and the metal backbone are both included within the outer conduitadjacent to the outer conduit distal end; (b)(ii) the metal backbonedistal portion transitions from a secondary shape that is uncoiled to aprimary shape that is coiled; and (b)(iii) the metal backbone distalportion is in the metal backbone distal portion secondary shape and islocated between the SMP foam distal end and the distal end of the outerconduit; advancing the system into a patient; deploying the metalbackbone distal end from the outer conduit distal end into a vessel ofthe patient; transitioning the metal backbone distal end from itssecondary shape to its primary shape; engaging the metal backbone distalend with a wall of the vessel in response to transitioning the metalbackbone distal end from its secondary shape to its primary shape;deploying the SMP foam from the outer conduit distal end into the vesselin response to deploying the metal backbone distal end from the outerconduit distal end; transitioning the SMP foam from its secondary shapeto its primary shape; engaging the SMP foam with the wall of the vesselin response to transitioning the SMP foam from its secondary shape toits primary shape; and occluding the vessel in response to engaging theSMP foam with the wall of the vessel.

Example 21a includes the method of example 20, wherein: the metalbackbone distal portion includes an outer metal portion, including achannel, and an inner metal portion included within the channel; atleast a portion of the outer metal portion is more radiopaque than boththe inner metal portion and the SMP foam; the method further comprisingdetermining a position of the SMP foam within the vessel in response toat least a portion of the outer metal portion being more radiopaque thanboth the inner metal portion and the SMP foam.

Example 22a includes the system of example 8 including a plurality ofresilient arm members that are free from one another at distal ends ofthe arm members and are fixedly coupled to each other at proximal endsof the arm members; wherein: the metal backbone first portion isgenerally aligned along an axis; at least a portion of the SMP foam islocated within the plurality of arms such that a plane orthogonal to theaxis intersects the SMP foam and the plurality of arms; the plurality ofarms compresses within the outer conduit and expands radially when thearms deploy from the outer conduit.

The foregoing description of the embodiments of the invention has beenpresented for the purposes of illustration and description. It is notintended to be exhaustive or to limit the invention to the precise formsdisclosed. This description and the claims following include terms, suchas left, right, top, bottom, over, under, upper, lower, first, second,etc. that are used for descriptive purposes only and are not to beconstrued as limiting. The embodiments of a device or article describedherein can be manufactured, used, or shipped in a number of positionsand orientations. Persons skilled in the relevant art can appreciatethat many modifications and variations are possible in light of theabove teaching. Persons skilled in the art will recognize variousequivalent combinations and substitutions for various components shownin the Figures. It is therefore intended that the scope of the inventionbe limited not by this detailed description, but rather by the claimsappended hereto.

1. A system comprising: an outer conduit having proximal and distalends; a shape memory polymer (SMP) foam having proximal and distal endsand that transitions from a secondary shape to a primary shape when theSMP foam is heated above its transition temperature; a metal backboneincluding: (a)(i) a first portion that extends from the SMP foamproximal end to the SMP foam distal end and which is generally coveredby the SMP foam, and (a)(ii) a distal portion that extends distally fromthe SMP foam distal end and which is not covered by the SMP foam;wherein: (b)(i) SMP foam and the metal backbone are both included withinthe outer conduit adjacent to the outer conduit distal end; (b)(ii) themetal backbone distal portion transitions from a secondary shape that isuncoiled to a primary shape that is coiled; and (b)(iii) the metalbackbone distal portion is in the metal backbone distal portionsecondary shape and is located between the SMP foam distal end and thedistal end of the outer conduit.
 2. The system of claim 1, wherein theSMP foam is a polyurethane SMP foam that includes N,N,N′,N′-tetrakis(2-hydroxypropyl) ethylenediamine (HPED), triethanolamine (TEA), andhexamethylene diisocyanate (HDI).
 3. The system of claim 2 wherein themetal backbone distal portion includes an outer metal portion, includinga channel, and an inner metal portion included within the channel. 4.The system of claim 3, wherein: the metal backbone first portion alsoincludes the inner metal portion but does not include the outer metalportion; and the inner metal portion is monolithic and extends from theSMP foam proximal end, to and through the SMP foam distal end, and intothe channel of the outer metal portion distal to the SMP foam.
 5. Thesystem of claim 4, wherein at least a portion of the outer metal portionis more radiopaque than both the inner metal portion and the SMP foam.6. The system of claim 5, wherein the inner metal portion issuperelastic.
 7. The system of claim 6, wherein: the SMP foam includes aproximal portion that includes the proximal end of the SMP foam and adistal portion that includes the distal end of the SMP foam; and one ofthe proximal and distal portions of the SMP foam fixedly adheres to themetal backbone first portion and another of the proximal and distalportions of the SMP foam slideably couples to the metal backbone firstportion.
 8. The system of claim 7, wherein the SMP foam and the metalbackbone distal portion are oriented with respect to each other and withrespect to the outer conduit so the metal backbone distal portiondeploys from the distal end of the outer conduit before the SMP foamdeploys from the distal end of the outer conduit.
 9. The system of claim8 comprising a proximal metal portion that is: (c)(i) coupled to theinner metal portion, (c)(ii) located proximal to the SMP foam, (c)(iii)included within the outer conduit, and (c)(iv) is more radiopaque thanboth the inner metal portion and the SMP foam.
 10. The system of claim8, wherein at least one of the proximal metal portion and metal backboneincludes an outer diameter that is at least 50% of an inner diameter ofthe outer conduit.
 11. The system of claim 8, wherein: the metalbackbone first portion is aligned along an axis; and the metal backbonedistal portion, in its primary shape, provides a radial force that isgenerally orthogonal to the axis and is greater than another radialforce exerted by the SMP foam.
 12. The system of claim 8, wherein theouter conduit includes an introducer sheath.
 13. The system of claim 8,wherein: the metal backbone first portion is aligned along an axis; andthe SMP foam and the metal backbone distal portion are oriented withrespect to each other so when upstream blood pressure forces the SMPfoam towards the metal backbone distal portion the metal backbone distalportion, in its primary shape, presses radially outwards in a directiongenerally orthogonal to the axis and in response to the upstream bloodpressure forcing the SMP foam towards the metal backbone distal portion.14. The system of claim 8 with the TEA contributing a lower molar ratioof hydroxyl groups to the polyurethane SMP foam than the HPED.
 15. Thesystem of claim 8 with the TEA contributing a higher molar ratio ofhydroxyl groups to the polyurethane SMP foam than the HPED.
 16. Thesystem of claim 15, wherein the polyurethane SMP foam includes adiisocyanate component consisting of the HDI and no other diisocyanatecomponent.
 17. The system of claim 8, wherein the outer metal portionincludes at least one of platinum, palladium, tungsten, and iridium. 18.The system of claim 8 comprising an additional outer metal portionproximal to the SMP foam and not covered by the foam, wherein: theadditional outer metal portion includes an additional channel; the innermetal portion extends to and through the SMP foam proximal end and intothe additional channel; and the inner metal portion that extends to andthrough the SMP foam proximal end and into the additional channel alsotransitions from a secondary shape that is uncoiled to a primary shapethat is coiled.
 19. The system of claim 8, wherein the metal backbonedistal portion primary shape that is coiled includes a conically shapedcoil with a base of the conically shaped coil between the SMP foam and avertex of the conically shaped coil.
 20. The system of claim 8 includinga plurality of resilient arm members that are free from one another atdistal ends of the arm members and are fixedly coupled to each other atproximal ends of the arm members; wherein: the metal backbone firstportion is generally aligned along an axis; at least a portion of theSMP foam is located within the plurality of arms such that a planeorthogonal to the axis intersects the SMP foam and the plurality ofarms; the plurality of arms compresses within the outer conduit andexpands radially when the arms deploy from the outer conduit.
 21. Amethod comprising: providing a system comprising: an outer conduithaving proximal and distal ends; a shape memory polymer (SMP) foamhaving proximal and distal ends and that transitions from a secondaryshape to a primary shape when the SMP foam is heated above itstransition temperature; a metal backbone including: (a)(i) a firstportion that extends from the SMP foam proximal end to the SMP foamdistal end and which is generally covered by the SMP foam, and (a)(ii) adistal portion that extends distally from the SMP foam distal end andwhich is not covered by the SMP foam; wherein: (b)(i) SMP foam and themetal backbone are both included within the outer conduit adjacent tothe outer conduit distal end; (b)(ii) the metal backbone distal portiontransitions from a secondary shape that is uncoiled to a primary shapethat is coiled; and (b)(iii) the metal backbone distal portion is in themetal backbone distal portion secondary shape and is located between theSMP foam distal end and the distal end of the outer conduit; advancingthe system into a patient; deploying the metal backbone distal end fromthe outer conduit distal end into a vessel of the patient; transitioningthe metal backbone distal end from its secondary shape to its primaryshape; engaging the metal backbone distal end with a wall of the vesselin response to transitioning the metal backbone distal end from itssecondary shape to its primary shape; deploying the SMP foam from theouter conduit distal end into the vessel in response to deploying themetal backbone distal end from the outer conduit distal end;transitioning the SMP foam from its secondary shape to its primaryshape; engaging the SMP foam with the wall of the vessel in response totransitioning the SMP foam from its secondary shape to its primaryshape; and occluding the vessel in response to engaging the SMP foamwith the wall of the vessel.
 22. The method of claim 21, wherein: themetal backbone distal portion includes an outer metal portion, includinga channel, and an inner metal portion included within the channel; atleast a portion of the outer metal portion is more radiopaque than boththe inner metal portion and the SMP foam; the method further comprisingdetermining a position of the SMP foam within the vessel in response toat least a portion of the outer metal portion being more radiopaque thanboth the inner metal portion and the SMP foam.